Treatment Options For Localized Scleroderma

J Dutz, MD, FRCPC
Divisions of Dermatology and Rheumatology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

ABSTRACT

Localized scleroderma, or morphea, is a chronic disease that causes a thickening and induration of the skin. For plaque type morphea, the treatments of choice include super-potent corticosteroids and calcipotriol. For the more generalized forms, as well as the linear forms, UVA is currently the best therapeutic modality. Patients with localized scleroderma are managed by both rheumatologists and dermatologists. There is still much therapeutic uncertainty in this disease.

Localized scleroderma (LS), or morphea, has been classified into plaque, generalized, linear, and deep forms1. The natural progression of the plaque form of LS is of a gradual softening to spontaneous resolution after a mean duration of 4 years with the plaque group having the shortest period of activity and the deep form the longest2. Significant disability occurs in both linear and deep forms of morphea. Both the plaque and generalized forms can also be disfiguring, since spontaneous resolution does not invariably occur. To prevent such outcomes, clinicians use topical corticosteroids, antimalarials, etretinate, penicillin, D-penicillamine, phenytoin, vitamin E and griseofulvin. Because none of these have been used in controlled studies, favorable improvement due to spontaneous resolution cannot be excluded3.

Use of Ultraviolet A

Published reports suggest that high dose UVA1 may be the most efficacious form of light treatment followed in order, by low-dose UVA1, and UVA in conjunction with topical and systemic psoralens (PUVA) (see Table 1). UVA and UVA1 treatment have yet to be compared clinically. However, the potential long-term toxicity of long wave UVA is still unknown, and its light sources are not readily available in North America. Further, the long-term oncogenic potential of PUVA is well documented. Given the propensity for skin thickening to improve, double-blind, controlled, randomized studies are needed to confirm the efficacy of these treatment modalities.

Use of vitamin D derivatives

Calcitriol has an antisynthetic and antiproliferative effect on fibroblasts from sclerodermatous skin. Oral calcitriol also has a beneficial effect on localized scleroderma mediated through immune or local effects. Regular monitoring for hypercalcemia and hypercalciuria is required. A serial renal ultrasound may be required to detect potential nephrocalcinosis13. Calcipotriol/calcipotriene, a calcitriol analogue, has also been shown to inhibit the growth of fibroblasts from sclerodermatous skin.

Use of Systemic Immunomodulation

Because immune cell activation is believed to underlie the development of skin sclerosis, systemic immunosuppressants have been used to treat severe and refractory localized scleroderma. Methotrexate is a folic acid analogue with multiple anti-inflammatory effects and has been found to be beneficial for treatment of morphea.

Treatment

Morphea type

Numbers treated

Dose and duration

Outcome

Calcitriol20,21,27
(Oral)

G
D
L

2
2
7

0.25 – 1.25 µg OD for 3 – 10.5 months

Improved ↑ urinary calcium 6/7 improved

Calcipotriol22, 23
(Topical)

P/G and L

12

Nightly occlusion with ointment (0.005%) BID for 3 months

52% improvement in skin score

L

1

Cream (0.005%) BID for 6 months

50% decrease in surface area

Corticosteroids have been used systemically to treat severe disease. Treatment with antimalarials15,16, azathioprine17, sulfasalazine18, and D-penicillamine24 has also been described in anecdotal fashion. Use of combination antimalarial therapy, i.e., quinacrine with hydroxychloroquine or chloroquine, can be of benefit in patients with cutaneous lupus refractory to single agent therapy alone19. This may be a safe and worthwhile strategy in generalized morphea. These immunosuppressive drugs have potential side-effects and appropriate monitoring is required.

Table 3: Larger case series of morphea patients treated with other medications. Benefits claimed by any of these therapeutic options have been substantiated by proper clinical trials (cited above).

Summary and an approach to treatment

The clinician is faced with considerable uncertainty when choosing a treatment modality for localized scleroderma. Given the benign natural progression of plaque type morphea, treatment with topical modalities such as super-potent corticosteroids or calcipotriol is prudent. Although no studies of the effectiveness of topical corticosteroids in localized morphea have been published, these agents have been shown to be very effective in lichen sclerosus et atrophicus, a clinically associated condition. For the more generalized forms and the linear forms, the use of UVA (either long wave alone or PUVA) is currently the best documented therapeutic modality. In the absence of access to these modalities and in the face of very active inflammatory disease involving deeper structures, oral calciferol or systemic immunosuppression may be contemplated. Recent studies support the use of methotrexate and systemic corticosteroids but controls are lacking. There remains a great amount of therapeutic uncertainty in this disease, and resolution must await the organization and completion of controlled/blinded multicenter therapeutic trials.